Table 2. Major Histopathological Categories of Non-Hodgkin Lymphoma in Children and Adolescentsa continued...

NHL observed in primary immunodeficiency usually shows a mature B-cell phenotype and large cell histology.[5] Mature T-cell lymphoma and anaplastic large cell lymphoma have been observed.[5] Children with primary immunodeficiency and NHL are more likely to have high-stage disease and present with symptoms related to extranodal disease, particularly the gastrointestinal tract and CNS.[5]

PTLD represents a spectrum of clinically and morphologically heterogeneous lymphoid proliferations. Essentially all PTLD following HSCT is associated with EBV, but EBV-negative PTLD can be seen following solid organ transplant.[47] The WHO has classified PTLD into the following three subtypes:[6]

Monomorphic PTLD – Histologies observed in the monomorphic subtype are similar to those observed in NHL, with diffuse large B-cell lymphoma being the most common histology, followed by Burkitt lymphoma, with myeloma or plasmacytoma occurring rarely.

The B-cell stimulation by EBV may result in multiple clones of proliferating B cells, and both polymorphous and monomorphous histologies may be present in a patient, even within the same lesion of PTLD.[48] Thus, histology of a single biopsied site may not be representative of the entire disease process. Not all PTLD is B-cell phenotype.[6] EBV lymphoproliferative disease posttransplant may manifest as isolated hepatitis, lymphoid interstitial pneumonitis, meningoencephalitis, or an infectious mononucleosis-like syndrome. The definition of PTLD is frequently limited to lymphomatous lesions (low stage or high stage), which are often extranodal (frequently in the allograft).[47] Although less common, PTLD may present as a rapidly progressive, high-stage disease that clinically resembles septic shock, which almost always results in death despite therapy.[49]

Rare NHL occurring in children

Low- or intermediate-grade mature B-cell lymphomas, such as small lymphocytic lymphoma, MALT lymphoma, mantle cell lymphoma, myeloma, or follicular cell lymphoma, are rarely seen in children. The most recent WHO classification has identified pediatric follicular lymphoma and pediatric nodal marginal zone lymphoma as unique entities.[1]